We request continued support for the Yale Cancer Center and the continued recognition as an NCI designated comprehensive cancer center. The major focus of the Center is in molecular medicine and the application of the new biology into the clinics to bring about progress in the prevention, diagnosis and treatment of cancer. In this application we request support for 14 research programs, five of which are new restructured programs focusing on specific diseases or scientific thrusts that bridge laboratory and clinical research efforts (Cancer Genetics, Genetic Therapy/Medical Oncology and Hematology, Stem Cell Biology and Transplant, Breast Cancer Research Lymphoma Research), and 14 shared resources, six of which are new since the last application (Biostatistics, Medical Informatics, Rapid Case Ascertainment, Genetic Therapy Human Applications, Genetic Counseling and Gene Targeting Service). In addition a new research program on prostate cancer has been established and supported by YCC, and three former research programs and one shared resource have been phases out. Since the last application a strong recruiting effort has led to restaffing of several YCC programs, and changes in leadership and administrative structure of the Center. We request support for the senior leadership, program directors at a level that reflects their actual time commitment to the center and its programs and for sufficient administrative staff to ensure the continued smooth functioning of the YCC and its evolution as a comprehensive cancer center. The YCC has a robust research base of a total of $54 million dollars in peer reviewed funding of which $13.9 million dollars comes from NCI grants exclusive of the CCSG. Since the last submission major changes have also resulted in a more substantial clinical trials program with strong support for data management and Biostatistics and the establishment of a clinical trials network (The Yale Oncology Network or YON), that will allow the YCC members the flexibility to test the impact of their research results on the practical applications for people with cancer in the YCC catchment area including the undeserved populations in the sphere of influence of YON institutions.